PubMed Health⌕ Search

Biomedical subjects

John Abraham

Publications and source records attributed to John Abraham.

17 recordsLinked to original sources
PubMed2006

Testing times: the emergence of the practolol disaster and its challenge to British drug regulation in the modern period.

This article analyses how practolol, the first British drug disaster of the modern, post-thalidomide regulatory period, related to the pharmaceutical industry, the medical profession and government regulation of patients' health. Drawing on comparison with the USA, it argues that, contrary to public expectation and perception, the aftermath of thalidomide did not give rise to strident British drug control, imposing the highest possible safety standards on the pharmaceutical industry. Rather, there existed a culture of reluctant regulation that was characterised by continued optimism about, and trust in the purported benefits of new drugs among manufacturers and regulators in the United Kingdom, together with commitment to the protection of the industry and its institutional support for the medical profession. In particular, British regulators were willing to allow new drugs on to the market, fully aware of uncertainty about their safety, but unwilling to be pro-active in issuing warning letters about risks and requiring 'certainty' before acting to withdraw a product. Even after the practolol disaster, the British system was unable to reform itself to construct more rigorous and pro-active monitoring of drug risks. This was because of conflicts with industry interests.

Adrenergic beta-Antagonists↗
PubMed2005

Lattice Boltzmann model for axisymmetric multiphase flows.

A lattice Boltzmann model is presented for axisymmetric multiphase flows. Source terms are added to a two-dimensional standard lattice Boltzmann equation for multiphase flows such that the emergent dynamics can be transformed into the axisymmetric cylindrical coordinate system. The source terms are temporally and spatially dependent and represent the axisymmetric contribution of the order parameter of fluid phases and inertial, viscous, and surface tension forces. A model which is effectively explicit and second order is obtained. This is achieved by taking into account the discrete lattice effects in the Chapman-Enskog multiscale analysis, so that the macroscopic axisymmetric mass and momentum equations for multiphase flows are recovered self-consistently. The model is extended to incorporate reduced compressibility effects. Axisymmetric equilibrium drop formation and oscillations, breakup and formation of satellite droplets from viscous liquid cylindrical jets through Rayleigh capillary instability, and drop collisions are presented. Comparisons of the computed results with available data show satisfactory agreement.

Journal Article↗
PubMed2005

Lattice Boltzmann methods for binary mixtures with different molecular weights.

Previous authors have suggested lattice Boltzmann methods for binary mixtures. However, these methods are limited to fluids with nearly the same molecular weight. In this work, two modified methods are proposed for simulating fluids with different molecular weights. The first method is based upon the physical principle that particles with different molecular weights move at different lattice speeds (DLS) when at the same temperature. Therefore, different streaming distances are employed for species with different molecular weights. A second method is developed by selecting constants in the equilibrium distribution function in such a way that the speed of sound can be adjusted for each species. In this approach, the species have the same lattice speed (SLS). Using multiscale expansions, the methods are shown to reproduce the appropriate species continuity equation in the macroscopic limit. The accuracy of the methods is evaluated by studying binary diffusion problems. The DLS method is shown to be able to simulate diffusion in fluids with larger ratios of molecular weights relative to the SLS method.

Journal Article↗
PubMed2005

Multiple-relaxation-time lattice-Boltzmann model for multiphase flow.

The lattice-Boltzmann method has shown promise in simulating multiphase flows. However, when using the Bhatnagar-Gross-Krook (BGK) collision operator and polynomial equilibria, numerical stability problems have been shown to occur as the relaxation time is decreased. Some authors have suggested the use of multiple-relaxation-time (MRT) models in lieu of the BGK collision operator, which employs a single relaxation time, to enhance numerical stability. In this paper, a MRT lattice-Boltzmann model for multiphase flow is developed and evaluated for accuracy in several test problems including oscillating liquid cylinders and capillary waves. It is shown that the MRT model is able to achieve numerically stable results at lower viscosities relative to the corresponding BGK model.

Journal Article↗
PubMed2005

A comparative analysis of drug safety withdrawals in the UK and the US (1971-1992): implications for current regulatory thinking and policy.

By going beyond individual case studies and solely quantitative surveys, this paper systematically examines why there were over twice as many new prescription drugs withdrawn from the market on grounds of safety in the UK as there were in the US between 1971 and 1992. Drawing on interviews with regulators, industry scientists and others involved, and on regulatory data never before accessed outside governments and companies, five key hypotheses which might explain this difference in drug safety withdrawals are analysed. These are: (1) simply because the UK approved more new drugs than the US; (2) because of an industrial corporate strategy to seek approval of 'less safe' drugs in the UK earlier; (3) because British regulators were more vigilant at spotting post-marketing safety problems than their US counterparts; (4) because the slowness of the US in approving new drugs enabled regulators there to learn from, and avoid, safety problems that had already emerged in the UK or European market; and (5) because more stringent regulation in the US meant that they approved fewer unsafe drugs on to the market in the first place. It is concluded that the main explanation for fewer drug safety withdrawals in the US is that the regulatory agency there applied more stringent pre-market review and/or standards, which took longer than UK regulatory checks, but prevented unsafe drugs marketed in the UK from entering the US market. Contrary to the claims frequently made by the pharmaceutical industry and regulatory agencies on both sides of the Atlantic, these results imply that it is likely that acceleration of regulatory review times in the US and the UK since the early 1990s is compromising drug safety.

Consumer Product Safety↗
PubMed2004

Pharmaceuticals, the state and the global harmonisation process.

This article examines how regulatory agencies' mission to protect and promote public health, enshrined in legislation, has been shaped and limited by commitments to the commercial interests of the pharmaceutical industry. It is argued that the regulatory state has become largely a 'competition state' which considers its primary role to be the maintenance of industry's competitive position in world markets. By examining regulatory developments across the EU, Japan and the US, I shall explain how the competition state became a building block for the global harmonisation process. To legitimise the global harmonisation process in terms of their mission to protect and promote public health, regulators claim that it does not lower safety standards and will accelerate the availability of pharmaceutical innovations to patients who need them. However, evidence is presented to suggest that these legitimising claims are not tenable.

Adverse Drug Reaction Reporting Systems↗
PubMed2003

Reshaping the carcinogenic risk assessment of medicines: international harmonisation for drug safety, industry/regulator efficiency or both?

The most significant institutional entity involved in the harmonisation of drug testing standards worldwide is the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), which comprises the three pharmaceutical industry associations and regulatory agencies of the EU, US and Japan. It is often claimed that such harmonisation will both accelerate the development and approval of new drugs and preserve safety standards, if not strengthen safety regimes. Drawing on extensive documentary research and interviews, this paper systematically examines whether the efforts by the ICH to improve industrial and regulatory efficiency by harmonising drug testing requirements is likely to raise, maintain or compromise safety standards in carcinogenic risk assessment of pharmaceuticals. The evidence suggests that, in the field of carcinogenicity testing, the ICH management of international harmonisation of medicines regulation is not achieving simultaneous improvements in safety standards and acceleration of drug development. Rather, the latter is being achieved at the expense of the former. Indeed, the ICH may be converting permissive regulatory practices of the past into new scientific standards for the future. These findings are significant as many expert scientific advisers to drug regulatory agencies seem to have accepted uncritically the conclusions reached by the ICH, which may affect a potential patient population of half a billion and tens of thousands of clinical trials.

Animals↗
PubMed2003

The science and politics of medicines control.

Drug development and regulation are often presented as purely matters of technical science. In this paper it is argued that, in principle, toxicology, clinical pharmacology and pharmacovigilance in drug testing and regulation are necessarily a combination of science and politics. This has important implications for how one attempts to make progress in drug regulation, such as in interpreting technical evidence and in the setting of regulatory standards with which evidence should be evaluated. In practice, drug testing and regulation are shown to be hybrids of science and politics. Moreover, drawing on existing empirical evidence, it is suggested that this mixture currently, and for some time, has had the wrong ingredients for optimal drug safety and public health outcomes. For example, too often the balance of the scientific doubts about drug safety are weighed to the interests of manufacturers rather than to those of patients and public health, while some scientific standards with which drug safety is to be interpreted are being reshaped in ways that give insufficient priority to the protection of public health. Finally, it is proposed that: drug regulation should include comparative efficacy testing; regulatory agencies should conduct some key tests, charging the costs to industry and without duplication; and the regulatory system should be less secretive and more accountable to public scrutiny. Greater efforts should be made to eliminate experts' conflicts of interest within the regulatory process.

Animals↗
PubMed2002

The pharmaceutical industry as a political player.

The pharmaceutical industry has produced many drugs that have benefited man. Political frameworks designed to govern the industry must maintain these benefits. However, regulation needs to be sufficiently robust to protect public health from drugs that are unsafe, ineffective, or unnecessary. The extent of industry influence over drug regulation, at the expense of other interested parties, suggests that the current system could be more robust. The many ways in which the pharmaceutical industry can influence governments and regulatory agencies are discussed, and methods by which this influence can be curbed are suggested.

Conflict of Interest↗
PubMed2002

Transnational industrial power, the medical profession and the regulatory state: adverse drug reactions and the crisis over the safety of Halcion in the Netherlands and the UK.

Taking the controversy over the safety of the hypnotic, Halcion, in the Netherlands and the UK, as a case study, this article examines the problems for public health associated with responses to warnings about drug hazards by regulatory agencies, governmental expert advisers, the pharmaceutical industry and the medical profession. It is argued that regulators and the medical profession rely too heavily on manufacturers to investigate warnings from doctors' spontaneous reporting of adverse effects of drug products on the market. It is demonstrated that a pharmaceutical firm's commitment to search effectively for evidence against the safety of its own product in order to confirm doctors' warnings can have severe limitations. Deficiencies in the socio-institutional responses to post-market 'early warning systems' about drug hazards imply that the regulatory policies of 'early licensing' and minimal pre-market checks for new drugs are misconceived and threaten public health. To improve public protection from drug injury, the regulators should abandon their conviction that compelling evidence of drug hazards are required to confirm doctors' warning signals prior to regulatory intervention. Instead, they should adopt a policy of measured regulatory intervention as an immediate response to warning signals, while investigators, independent of the manufacturers, assess the significance of the signal.

Adverse Drug Reaction Reporting Systems↗
PubMed2002

Progress, innovation and regulatory science in drug development: the politics of international standard-setting.

This paper examines international standard-setting in the toxicology of pharmaceuticals during the 1990s, which has involved both the pharmaceutical industry and regulatory agencies in an organization known as the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The analysis shows that the relationships between innovation, regulatory science and 'progress' may be more complex and controversial than is often assumed. An assessment of the ICH's claims about the implications of 'technical' harmonization of drug-testing standards for the maintenance of drug safety, via toxicological testing, and the delivery of therapeutic progress, via innovation, is presented. By demonstrating that there is not a technoscientific validity for these claims, it is argued that, within the ICH, a discourse of technological innovation and scientific progress has been used by regulatory agencies and prominent parts of the transnational pharmaceutical industry to legitimize the lowering and loosening of toxicological standards for drug testing. The mobilization and acceptance of this discourse are shown to be pivotal to the ICH's transformation of reductions in safety standards, which are apparently against the interests of patients and public health, into supposed therapeutic benefits derived from promises of greater access to more innovative drug products. The evidence suggests that it is highly implausible that these reductions in the standards of regulatory toxicology are consistent with therapeutic progress for patients, and highlights a worrying aspect embedded in the 'technical trajectories' of regulatory science.

Drug Industry↗
PubMedDate not supplied

Carotid artery imaging in the United kingdom: a postal questionnaire of current practice.

There has been a steady rise in the use of carotid duplex imaging in the selection of patients for carotid endarterectomy (CEA). Some would suggest that CEA could be safely performed without preoperative contrast angiography. The purpose of this study was to focus on the role of duplex imaging among vascular surgeons in the United Kingdom and to highlight current practices in imaging prior to CEA. A postal questionnaire was sent to all consultant members of the Vascular Surgical Society of Great Britain and Ireland about the choice of imaging prior to selection of patients for CEA, preoperative imaging, and choice of imaging (if any) in the confirmation of carotid occlusion indicated by duplex scanning. Of 396 questionnaires sent, 323 (82%) were returned. Of these, 259 (80%) consultants performed carotid surgery, 118 (45%) in university hospitals (UHs) and 141 (53%) in district general hospitals (DGHs). One hundred eighteen (100%) and 137 (97%) respondents, respectively, chose duplex scanning as their first-line investigation. Sixty (51%) respondents in UHs and 49 (35%) respondents in DGHs repeated duplex scanning immediately preoperatively, with 57 (95%) and 46 (94%), respectively, using duplex scanning. Forty-seven (40%) respondents in UHs and 78 (55%) respondents in DGHs would reconfirm an occlusion, with 30 (64%) and 48 (62%), respectively, using computed tomography and magnetic resonance imaging as their preferred tool. Our study shows that duplex scanning is the first-line imaging technique for patient selection for CEA by vascular surgeons in the United Kingdom. Magnetic resonance imaging and computed tomography are replacing conventional angiography where duplex scanning is equivocal.

Arterial Occlusive Diseases↗